Therapeutic use of [131I]metaiodobenzylguanidine in neuroblastoma: a phase II study in 26 patients. "Société Fran?aise d'Oncologie Pédiatrique" and Nuclear Medicine Co-investigators.

Seven French Medical Centers were involved in a cooperative study evaluating [131I]Metaidobenzylguanidine (131I-MIBG) therapy in advanced neuroblastoma. Children (median age 4 years) had initially a stage III (4 patients) or stage IV (22 patients) neuroblastoma. Before MIBG treatment, 14 patients had a primarily refractory disease, 10 patients were relapsing; in 8 cases, autologous bone marrow transplantation had been performed. Tumour sites were in 24 patients: 13/24 local disease, 8/24 bone metastases, and 7 bone marrow involvement. Catecholamines were elevated in 7/24 patients. The median activity of 131I-MIBG per injection ranged from 30 to 108 mCi; the number of injections varied from 1 to 5. We observed 5/10 pain palliations and 10/24 stabilizations of the disease course for 1 to 7 months with no objective volume tumour response. Haematologic toxicity caused a platelet count less than 150,000/microL in 4 patients, less than 100,000 in 1 patient and less than 50,000 in 7 patients.     

c-AMP and Morphogenesis of Acetabularia

The c-AMP content has been found to double when Acetabularia develop from 5–10 mm long to grown or almost full-grown algae.
The biological significance of this fact has been approached by studying the effects of drugs known to influence the intracellular c-AMP content on the development of Acetabularia. When grown in the presence of theophyllin or papaverin, inhibitors of phosphodiesterase, the Acetabularia display a striking response during the exponential growth period; the final length, however, is not affected. Both substances increase the c-AMP content of the algea. Isoproterenol, which activates adenylate cyclase in many systems, also influences Acetabularia during the exponential growth period and, in addition, slightly affects cap formation.
The change in c-AMP content in the course of development and the effects of drugs influencing (theophyllin and papaverin) or likely to influence (isoproterenol) the c-AMP content of the algae suggest that this nucleotide plays a role at the time of intense growth.
The same phosphodiesterase activity has been found in the 5–10 mm and the 19–25 mm long algae, whereas two enzymes were found in cap-bearing Acetabularia.
The results are discussed as well as the involvement of c-AMP in the development of this alga.     

131I]metaiodobenzylguanidine therapy in 20 patients with malignant pheochromocytoma.

Twenty patients, 16 male and 4 female (aged 11-76 years), with metastatic pheochromocytoma were treated in our Institution between 1985 and 1990. Metastases occurred in all patients: at presentation in 11 patients, with a 10 to 30 month delay in 7 patients, and 9 and 28 years later respectively in 2 patients. Catecholamines hyperproduction was present in all patients. Metaiodobenzylguanidine (MIBG) uptake was found in 16 patients after a diagnostic dose and only after a therapeutic dose in 1 patient. Surgery was performed on primary tumor (18 patients) and on distant metastases (10 patients). 131I-MIBG therapy was performed in 11 patients, 9 of whom were evaluable. The cumulative activity ranged from 3.7 to 26.3 GBq (100 to 711 mCi) in 1 to 6 courses. We observed symptomatic improvement (5 patients) and partial tumor response in 2 patients, which lasted for 28 and 9 months respectively, terminating with a rapidly progressing disease involving the bone marrow. Stabilisation was observed in 3 patients. Moderate myelosuppression occurred in 4 patients. Fifteen patients died with a median survival of 16 months (range 3-60). Response to therapy was poor and further evaluation of the presently available therapeutic approaches is needed.